Main B‐cell epitopes of PvAMA‐1 and PvMSP‐9 are targeted by naturally acquired antibodies and epitope‐specific memory cells in acute and convalescent phases of vivax malaria

Abstract

Although antibodies are considered critical for malaria protection, little is known about the mechanisms/factors that maintain humoral immunity, especially regarding the induction and maintenance of memory B cells over time. In Brazilian endemic areas, this is the first time that the profile of antibody responses and the occurrence of antigen‐specific memory B cells (MBC) against P vivax were investigated during acute malaria and up to six months after parasite clearance. For this, we selected two peptides, PvAMA‐1(S290‐K307) and PvMSP‐9(E795‐A808), which represent the apical membrane antigen‐1 and merozoite surface protein‐9 of P vivax, respectively. Both peptides were previously described as containing linear B‐cell epitopes. Our findings were as follows: 1—both peptides were recognized by IgG antibodies at a high frequency (between 24% and 81%) in all study groups; 2—in the absence of infection, the IgG levels remained stable throughout 6 months of follow‐up; and 3—PvAMA‐1(S290‐K307) and PvMSP‐9(E795‐A808)‐specific MBCs were detected in all individual groups in the absence of reinfection throughout the follow‐up period, suggesting long‐lived MBC. However, no positive association was observed between malaria‐specific antibody levels and frequency of MBCs over time. Taken together, these results suggest that peptides can be, in the future, an alternative strategy to polypeptidic vaccine formulation.

HIV infection increases the risk of acquiring Plasmodium vivax malaria: a 4-year cohort study in the Brazilian Amazon HIV and risk of vivax malaria

“…A mixed pattern of proinflammatory and regulatory biomarkers involving a robust IL-10 and IL-6 axis is produced in P. vivax malaria 43 and, in recurrent P. vivax episodes, an unbalanced CD4 + /CD8 + T-cell ratio was found and is associated with a significant increase in IL-10 levels 44 . Genetic polymorphisms in TLRs play a role in P. vivax susceptibility and parasitemia 42 , possibly by activation of IL-6, IFN-γ, IL-10 pathways 45 . From an integrated perspective, mechanisms behind recurrences and subclinical P. vivax infections are related to inhibitory receptors, T regulatory cells, and IL‐10, with a poor induction of immunological memory cells and inefficient T effector cells 46 .…”

New highly antigenic linear B cell epitope peptides from PvAMA-1 as potential vaccine candidates

“…Data from previous studies carried out with rodents and non-human primates have shown that Pv AMA-1 has already proved to be a promising target for inducing a protective immune response [ 10 , 11 , 35 ]. Several of them have confirmed its immunogenicity, especially in endemic areas such as the Brazilian Amazon [ 36 – 38 ]. In addition, the functionality of AMA-1-related antibodies has also been assessed.…”

Longitudinal IgG antibody responses to Plasmodium vivax blood-stage antigens during and after acute vivax malaria in individuals living in the Brazilian Amazon

“…Ethics statement. The original study for the collection of human studies was approved by the Institutional Review Board (IRB) of the Federal University of Juiz de Fora, Brazil (protocol #262.875/2013) [15]. Written informed consent was obtained from all the study participants.…”